SUMMARY. Being obese has been considered protective for osteoporosis and fragility fractures, partly because bone mineral density generally increases concomitantly with increasing BMI. However, recent evidence suggests that obese patients may not be protected from fracture risk, especially at sites other than hip, and new pilot data presented in this application suggest that fracture risk may actually be much higher in the severely obese (BMIe35) than normal-weight persons, with pathological fractures occurring at earlier ages. A significant number of severely obese are now choosing gastric bypass surgery as a treatment for obesity co- morbidities such as diabetes. This surgical procedure produces significant and sustained weight loss through a combination of gastric restriction and intestinal malabsorption, which may negatively impact the uptake of bone-related nutrients and eventually result in increased fracture risk compared with presurgical risk. In addition, post-surgery weight loss leads to muscle loss, often resulting in balance and strength problems. It is possible that a history of severe obesity, followed by malabsorptive surgery and subsequent muscle weakness and balance, poses an additive fracture risk. On the other hand, returning to a more normal body weight might alleviate the fracture risk attributed to severe obesity, with no additional risks coming from malabsorption. No long-term study has investigated fracture risk in the severely obese, and existing post-bariatric surgery fracture data are limited to only a few years of follow-up of small numbers of subjects. This lack of conclusive data on fracture risks limits evidence-based decision making for the growing number of severely obese evaluating bariatric surgery for weight loss and for the physicians providing continued care to post-surgical patients. The existing Utah Population Database (UPDB) of 15 million people, which links over 85% of Utah residents to their vital statistics, demographic data, and medical records with an average 16-year follow-up (range 1-32 years), will be analyzed to assess fracture incidence in severely obese patients with and without gastric bypass surgery. Over 15,000 gastric bypass surgery records from 1980-2012 are being merged to UPDB to provide statewide coverage. Site-specific and overall fracture rates in the severely obese with and without gastric bypass surgery will also be compared with normal-weight, overweight, and obese control subjects. The results of these analyses will better inform patients and physicians on the potential risks and/or benefits of gastric bypass surgery as a treatment option for severe obesity and may provide the basis of recommendations for more intensive long-term post-surgical follow-up of risk factors associated with fractures. Should these R21 database analyses confirm increased fracture rates in the severely obese after gastric bypass surgery, a detailed follow-up study will be proposed to actually measure bone mineral density and structure, balance, muscle strength, dietary intake, vitamin and mineral supplementation, and medication usage in a subset of these subjects to delineate the ultimate causes of increased fractures.